Abstract

BACKGROUND & AIMS:

During the last 15 years, several single-gene mendelian disorders have been discovered that might account for some of the familial aggregation detected in large population studies of colorectal cancer (CRC). Mutations in DNA mismatch repair (MMR) genes cause hereditary nonpolyposis colorectal cancer-Lynch syndrome, the most common of the recognized CRC-predisposition syndromes, in which one major feature is a young age for cancer onset. However, for young-onset microsatellite stable (MSS) CRC, the familial risk for CRC is unknown.

METHODS:

Patients with CRC who were <50 years old were identified through Minnesota Cancer Surveillance System (MCSS) and Mayo Clinic, Rochester, MN. CRCs in which the DNA MMR function was deficient as evidenced by high level microsatellite instability and/or loss of expression of MMR gene product by immunostaining were excluded. A total of 278 probands (131 from MCSS; 147 from Mayo Clinic) were included. Data on 1862 relatives were collected, of whom 68 were found to have had CRC, and an additional 165 had primary cancers of other types.